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Background@#We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. @*Methods@#We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. @*Results@#Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). @*Conclusion@#We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.
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Background@#We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. @*Methods@#We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. @*Results@#Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). @*Conclusion@#We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.
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Cytophagic histiocytic panniculitis (CHP) is a rare form of panniculitis, presenting lymphohistiocytic infiltration within subcutaneous fat tissue with phagocytic histiocytes. Associated systemic symptoms includes fever, hepatosplenomegaly, lymphadenopathy, serositis, pancytopenia, hepatic abnormalities, hypertriglyceridemia, and coagulopathy, which are the features of hemophagocytic lymphohistiocytosis (HLH). The patients of CHP associated with HLH may have nonfatal acute/intermittent, or rapidly fatal clinical courses, so the prompt and accurate diagnosis with immunosuppressive treatments are significant.
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Background@#There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. @*Materials and Methods@#We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. @*Results@#Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0). @*Conclusion@#The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR
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Background@#There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. @*Materials and Methods@#We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. @*Results@#Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0). @*Conclusion@#The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR
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BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.
Subject(s)
Humans , Cell Transplantation , Classification , Consolidation Chemotherapy , Induction Chemotherapy , Leukemia, Myeloid, Acute , Multivariate Analysis , Patient Selection , Protein-Tyrosine Kinases , Retrospective Studies , TransplantsABSTRACT
BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.
Subject(s)
Child , Humans , Anti-Bacterial Agents , Antibiotic Prophylaxis , Cicatrix , Demography , Medical Records , Multivariate Analysis , Retrospective Studies , Risk Factors , Trimethoprim, Sulfamethoxazole Drug Combination , Urinary Tract Infections , Urinary Tract , Vesico-Ureteral RefluxABSTRACT
In patients with acute myeloid leukemia (AML), pleural effusion may be attributed to various factors, including infection, hypoalbuminemia, and renal failure. However, leukemic infiltration of the pleural fluid is rarely reported and poorly understood. Extramedullary diseases have been reported with increasing frequency as the survival rates of patients with AML have increased. However, the reported prognostic effects of leukemic pleural effusion in patients with AML range from none to a worse prognosis. Here, we report a case of acute promyelocytic leukemia (APL) in a patient exhibiting leukemic pleural effusion with fluorescence in situ hybridization (FISH) results indicating the presence of the PML-RARA fusion gene. A 52-year-old man presented with pancytopenia, dyspnea, and fever. He had a medical history of hypertension, end-stage renal disease, and hepatitis B virus-related liver cirrhosis. A peripheral blood smear revealed the presence of multiple abnormally hypergranular promyelocytes. White blood cell differential counts were not performed due to severe pancytopenia. A bone marrow examination, immunophenotyping analysis, and cytogenetic and molecular studies revealed APL. The patient was treated with all-trans retinoic acid immediately after abnormal promyelocytes were observed in the peripheral blood smear, but induction chemotherapy was delayed because of his poor condition. His persistent dyspnea and abdominal discomfort led to a thoracentesis and the observation of abnormal promyelocytes that were positive for PML-RARA fusion gene by FISH. To our knowledge, this is the first report of leukemic pleural infiltration with PML-RARA fusion gene-positivity via FISH.
Subject(s)
Humans , Middle Aged , Bone Marrow Examination , Cytogenetics , Dyspnea , Fever , Fluorescence , Granulocyte Precursor Cells , Hepatitis B , Hypertension , Hypoalbuminemia , Immunophenotyping , In Situ Hybridization , Induction Chemotherapy , Kidney Failure, Chronic , Leukemia, Myeloid, Acute , Leukemia, Promyelocytic, Acute , Leukemic Infiltration , Leukocytes , Liver Cirrhosis , Pancytopenia , Pleural Effusion , Prognosis , Renal Insufficiency , Survival Rate , Thoracentesis , TretinoinABSTRACT
BACKGROUND: The Coapresta 2000 (CP2000; Seikisui, Japan) system is a fully-automated random-access multiparameter coagulation analyzer equipped with a photo-optical clot detection unit. It can perform clotting time assays as well as colorimetric assays. METHODS: We evaluated the analytical performance of CP2000 for several coagulation test parameters and compared its performance with that of the CA-7000 (Sysmex, Japan) system. Fresh and frozen plasma samples were used to evaluate the performance of CP2000 with respect to four routine coagulation test parameters: prothrombin time (PT), activated partial thromboplastin time, fibrinogen, and D-dimer. On-board stability of the liquid reagents was confirmed. Additionally, local international sensitivity index (ISI) verification was performed with four levels of calibrants and direct PT/international normalized ratio (INR) line. RESULTS: The intra- and inter-assay coefficients of variation were below 5% for every parameter in both normal and pathological ranges. Carryover was not detected. The results obtained using CP2000 showed good correlation (r 2 over 0.95) with those obtained by the CA-7000 analyzer. On-board stability in open-vial state, which was expected to be much longer than that of other reagents, was confirmed. Local verification of ISI showed an acceptable bias range of INR, compared with the values using calibrants. CONCLUSIONS: The high-throughput, CP2000 analyzer is a fast, user-friendly system with long on-board reagent stability. Its results were concordant with the CA-7000 analyzer, for analysis of the routine coagulation test parameters. Furthermore, this system would add greater confidence to the reporting of INR data.
Subject(s)
Bias , Fibrinogen , Indicators and Reagents , International Normalized Ratio , Partial Thromboplastin Time , Plasma , Prothrombin TimeABSTRACT
No abstract available.
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Leukemia, Plasma Cell , Plasma Cells , Plasma , PlasmacytomaABSTRACT
BACKGROUND: Recently, myeloproliferative leukemia (MPL) W515 mutations have been reported to be molecular markers for myeloproliferative neoplasms (MPNs). We studied the association between MPL W515 mutations and the clinico-hematological features of patients with MPNs. METHODS: Our study included 154 consecutive patients diagnosed with MPNs (31 had polycythemia vera [PV]; 106, essential thrombocythemia [ET]; and 17, primary myelofibrosis [PMF]). MPL W515 mutations were detected by real-time PCR and direct sequencing methods. RESULTS: The MPL W515L mutation was found in 4 patients and the MPL W515A mutation was detected in 1 patient. These 5 patients were diagnosed with JAK2 V617F-negative ET, and they accounted for 12.5% of patients with JAK2 V617F-negative ET. The patients with MPL W515-positive ET showed significantly lower hemoglobin levels and WBC counts than did patients with MPL W515-negative ET or JAK2 V617F-positive ET. CONCLUSIONS: MPL W515 mutation is a useful diagnostic marker for JAK2 V617F-negative MPNs and it is associated with specific hematologic characteristics such as lower hemoglobin levels and WBC counts.
Subject(s)
Humans , Janus Kinase 2 , Leukemia , Polycythemia Vera , Primary Myelofibrosis , Real-Time Polymerase Chain Reaction , Thrombocythemia, EssentialABSTRACT
BACKGROUND: The bacterium Chlamydia trachomatis is one of the leading causes of sexually transmitted diseases worldwide. Since no simple and effective tool exists to diagnose C. trachomatis infections, we evaluated a novel point-of-care (POC) test, aQcare Chlamydia TRF kit, which uses europium-chelated nanoparticles and a time-resolved fluorescence reader. METHODS: The test performance was evaluated by comparing the results obtained using the novel POC testing kit with those obtained using a nucleic acid amplification test (NAAT), using 114 NAAT-positive and 327 NAAT-negative samples. RESULTS: The cut-off value of the novel test was 20.8 with a detection limit of 0.27 ng/mL. No interference or cross-reactivity was observed. Diagnostic accuracy showed an overall sensitivity of 93.0% (106/114), specificity of 96.3% (315/327), positive predictive value (PPV) of 89.8% (106/118), and negative predictive value (NPV) of 97.5% (315/323). The sensitivity of the novel test was much higher than that of currently available POC tests. Furthermore, the relative ease and short turnaround time (30 min) of this assay enables C. trachomatis-infected individuals to be treated without a diagnostic delay. CONCLUSIONS: This simple and novel test is a potential tool to screen a larger population, especially those in areas with limited resources.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Chlamydia Infections/diagnosis , Chlamydia trachomatis/genetics , DNA, Bacterial/chemistry , Europium/chemistry , Metal Nanoparticles/chemistry , Point-of-Care Systems , Reagent Kits, Diagnostic , Real-Time Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
Laboratory values change with age and interpreting laboratory results from elderly people using the reference intervals for younger adults may not be appropriate. The authors investigated the distribution patterns of routine chemistry values from elderly people to determine whether current reference intervals are also valid for elderly people. A total of 1,215 persons older than 65 years and 1,827 healthy adults below 65 years of age were evaluated. Blood samples were collected after an overnight fast and analyzed for chemistry tests. Computing the central 95th percentile showed that the total protein, albumin, ALP, LD, creatinine, uric acid, triglyceride, HDL-cholesterol, and electrolytes of elderly people were within the standard reference intervals used in our laboratory. For AST and ALT, the upper range of the central 95th percentile in the elderly population was found to be outside the common reference interval. However, the central 90th percentile values of AST and ALT were compatible with the common reference intervals. GGT, BUN, total cholesterol, LDL-cholesterol, and glucose showed higher values than the upper limits of the reference intervals. For common clinical chemistry tests, the common reference values in general should be applicable to elderly people, even though some parameters showed wider distributions in the elderly.
Subject(s)
Adult , Aged , Humans , Chemistry, Clinical , Cholesterol , Clinical Chemistry Tests , Creatinine , Electrolytes , Glucose , Reference Values , Uric AcidABSTRACT
Exflagellation of the malaria parasite microgametocyte usually occurs in the gut cavity of Anopheles mosquitoes following an infective blood meal. Exflagellation is a very rare event in human blood. Due to its rarity, the appearance of this structure in a peripheral blood smear will easily create a diagnostic dilemma. We report a case of malaria with exflagellated microgametes in human blood that was initially mistaken for a double infection of Plasmodium and another blood flagellate. The patient was a 29-year-old Parkistani man presenting with fluctuating fever accompanied by chills and fatigue for 4 days. Initial peripheral blood smear examination showed a number of Plasmodium ring forms, trophozoites, and gametocytes. Additionally, several filamentous structures resembling blood flagellates were seen. With these features, an initial diagnostic impression of combined infection of malaria and blood flagellate was made. Later, we determined that these structures resembling blood flagellates were exflagellated microgametes of malarial parasite. Therefore, the knowledge that exflagellation may appear in human blood with Plasmodium species infection and being more familiar with differentiation of the morphologic features of other species infection can prevent further possible misinterpretation.
Subject(s)
Humans , Anopheles , Chills , Culicidae , Fatigue , Fever , Malaria , Meals , Parasites , Plasmodium , TrophozoitesABSTRACT
A malignant plasma cell clone usually produces a single abnormal monoclonal protein with a constant isotype. However, switching of paraprotein isotype has been reported to be a transient phenomenon associated with the recovery of B-cell function, and, in some cases, the switching might be misinterpreted as relapse. In August 2008, we encountered a case of a 59-year-old man with proteinuria and high IgG level (5.6 g/dL), kappa free light chain level of 2,660 mg/L, reversed A/G ratio (0.51), and multiple osteolytic lesions. Plasma cells, which accounted for 57% of all the nucleated cells, in bone marrow aspirates were positive for kappa immunostaining. Serum protein electrophoresis showed one M-spike, concentration of 4.87 g/dL in the beta region. Immunofixation electrophoresis revealed the peak as an IgG-kappa monoclonal protein; therefore, a diagnosis of plasma cell myeloma was made. Complete remission was achieved after chemotherapy, and autologous peripheral stem cell collection was performed. In March 2009, the patient underwent high-dose chemotherapy and autologous peripheral stem cell transplantation support. After 2 months, serum protein electrophoresis showed 2 M-spikes in the gamma region with positive IgM-lambda, IgG-lambda, and IgG-kappa, and these bands persisted. The electrophoretic mobility of the IgG-kappa protein was different from that of the original disease protein, and bone marrow results were the same as the previous ones. Although immunoglobulin isotype switch is known to have a benign course, it always requires careful monitoring because, in rare cases, true clonal switching may occur.